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Background: Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH. Methods: Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo. Results: PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo. Conclusions: Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH. [ABSTRACT FROM AUTHOR]

Background: In view of the high incidence of infantile hemangioma (IH) in infants and young children, a comprehensive and reasonable evaluation scale for referral is urgently needed. This study compared the influence of the Hemangioma Severity Scale (HSS) and the Infantile Hemangioma Referral Score (IHReS) on treatment decisions for infantile hemangioma patients. Objective: We aimed to establish a reliable and effective evaluation method for referral. Methods: This was a prospective study to determine whether treatment was needed for IH patients after evaluation with the HSS and IHReS. Results: A total of 266 consecutive referred IH patients were evaluated for the risk of IH, and the treatment rate was 80.8%. The area under the curve (AUC) of the subject receiver operating characteristic curve (ROC) of treatment decision making after referral by the HSS was 0.703 (95% CI: 0.634–0.772), and after referral by the IHReS was 0.892 (95% CI: 0.824–0.960). Limitations: This was a single-center study. Conclusions: For decisions regarding the treatment of IH patients, the IHReS has a higher efficiency and sensitivity than the HSS. However, the specificity of the IHReS is lower than that of the HSS. [ABSTRACT FROM AUTHOR]

Background: Infantile hemangioma (IH) is the most common benign tumor in children. Long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis. However, the expression levels and biological functions of lncRNAs in IH have not been well-studied. This study aimed to analyze the expression profile of lncRNAs and mRNAs in proliferating and involuting IHs. Methods: The expression profiles of lncRNAs and mRNAs in proliferating and involuting IHs were identified by microarray analysis. Subsequently, detailed bioinformatics analyses were performed. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analyses were conducted to validate the microarray results. Results: In total, 146 differentially expressed (DE) lncRNAs and 374 DE mRNAs were identified. The DE mRNAs were enriched mostly in angiogenesis-related biological processes (BPs) and pathways by bioinformatics analysis. In addition, metabolism-related BPs (e.g., "glycogen biosynthetic process" and "metabolic process") and pathways (e.g., "oxidative phosphorylation") were identified. A lncRNA-mRNA co-expression network was constructed from 42 DE lncRNAs and 217 DE mRNAs. Twelve lncRNAs were predicted to have cis-regulated target genes. The microarray analysis results were validated by qRT-PCR using 5 randomly selected lncRNAs and 13 mRNAs. The IHC results revealed that both LOXL2 and FPK-1 exhibited higher protein expression levels in proliferating IH than in involuting IH. Moreover, inhibition of PFK-1 could suppress hemangioma-derived endothelial cell proliferation and migration, induce cell arrest, and reduce glucose uptake and lactate and ATP production. Conclusions: The findings suggest that the identified DE lncRNAs and mRNAs may be associated with the pathogenesis of IH. The data presented herein can improve our understanding of IH development and provide direction for further studies investigating the mechanism underlying IH. [ABSTRACT FROM AUTHOR]

Background: Infantile hemangioma (IH) is the most common benign tumor in children. However, few studies have reported the clinical features of segmental IH. We aimed to determine the clinical characteristics of segmental IH and to identify features that may aid clinicians in managing segmental IH.Methods: In the cross-sectional prospective study approved by the Ethics Committee of the hospital, children diagnosed with IH were recruited, and information including patient demographics, IH morphology and anatomical location, complications and treatments were recorded and analyzed.Results: In total, 153 patients with segmental IH and 1375 patients with nonsegmental IH were enrolled in this study. The average age on the day of the first visit in patients with segmental IH was 3.63±3.23 months. In 69 patients (45.10%), segmental IH was diagnosed at birth. Most segmental IHs (49.67%) occurred in the limbs, while only 22.04% of nonsegmental IHs occurred in the extremities (P<0.001). Thirteen patients (8.50%) with segmental IH had ulceration. Compared with patients with nonsegmental IHs, patients with segmental IHs were more likely to be treated with oral drugs (P<0.001).Conclusion: Segmental IHs mainly occur in the extremities and are frequently diagnosed at birth. Segmental IHs are usually accompanied by ulceration, which are more commonly seen in the neck and perineal/perianal/genital areas than nonsegmental IHs. Oral propranolol is prescribed more often in patients with segmental IH than in those with nonsegmental IH. [ABSTRACT FROM AUTHOR]

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to be discovered. The main pathological features of KHE are abnormal angiogenesis and lymphangiogenesis. KHEs are clinically heterogeneous and may develop into a life-threatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). The heterogeneity and the highly frequent occurrence of disease-related comorbidities make the management of KHE challenging. Currently, there are no medications approved by the FDA for the treatment of KHE. Multiple treatment regimens have been used with varying success, and new clinical trials are in progress. In severe patients, multiple agents with variable adjuvant therapies are given in sequence or in combination. Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Novel targeted treatments based on a better understanding of the pathogenesis of KHE are needed to maximize patient outcomes and quality of life. This review summarizes the epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatments of KHE. Recent new concepts and future perspectives for KHE will also be discussed. [ABSTRACT FROM AUTHOR]

Aim: Kaposiform haemangioendothelioma (KHE) is a rare, potentially life-threatening vascular tumour that is often associated with thrombocytopenia and coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). Because of the rarity and complexity of KHE, the optimal paradigm for treating KHE has yet to be elucidated. We aim to assess the efficacy and safety of vincristine and sirolimus for the treatment of KHE.Methods: A comprehensive review of the literature was conducted from January 1993 to June 2018. A total of 15 studies were selected for the meta-analysis. Five studies included 75 individuals and reported the response and side effects to vincristine in the treatment of KHE with or without KMP. A total of 10 studies that included 127 individuals reported the response and safety of sirolimus for treating KHE with or without KMP.Results: The pooled odds ratio (OR) for the effectiveness of vincristine was 0.72. The pooled OR for the effectiveness of sirolimus was 0.91. The side effects associated with vincristine during the treatment included neuropathy, abdominal pain, loss of appetite and mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The side effects associated with sirolimus therapy included bronchitis; lymphopenia; elevated AST, ALT and platelets; hyperlipidaemia; opportunistic infection; mild reversible leukopenia; mucositis; fever; pain and skin rash/vomiting and diarrhoea.Conclusions: This systematic review showed a high efficacy of vincristine and sirolimus in the treatment of KHE. Based on the available data in the literature, it appears that sirolimus is potentially an efficacious and safe treatment option for KHE. Further randomised, controlled trials are recommended. [ABSTRACT FROM AUTHOR]

Background: Infantile hemangioma (IH) is the most common vascular tumor in children. It is controversial whether IHs has effects on the quality of life (QOL) in patients of whom IH poses no threat or potential for complication. Thus, we conducted this study to evaluate the q QOL in patients with IH and find the predictors of poor QOL.Methods: The PedsQL 4.0 Genetic Core Scales and the PedsQL family information form were administered to parents of children with IH and healthy children both younger than 2-year-old. The quality-of-life instrument for IH (IH-QOL) and the PedsQL 4.0 family impact module were administered to parents of children with IH. We compared the PedsQL 4.0 Genetic Core Scales (GCIS) scores of the two groups. Multiple step-wise regression analysis was used to determine factors that influenced QOL in children with IH and their parents.Results: Except for physical symptom, we found no significant difference in GCIS between patient group and healthy group (P = 0.409). The internal reliability of IH-QOL was excellent with the Cronbach's alpha coefficient for summary scores being 0.76. Multiple step-wise regression analysis showed that the predictors of poor IH-QOL total scores were hemangioma size, location, and mother's education level. The predictors of poor FIM total scores were hemangioma location and father's education level. The predictors of poor GCIS total scores were children's age, hemangioma location and father's education level.Conclusion: The findings support the feasibility and reliability of the Chinese version of IH-QOL to evaluate the QOL in children with IH and their parents. Hemangioma size, location and education level of mother are important impact factors for QOL in children with IH and their parents. [ABSTRACT FROM AUTHOR]